Down Syndrome and Aneuploidy Screening
What Is Down Syndrome?
Down syndrome is a chromosomal condition caused by the presence of an extra copy of chromosome 21. Normally, humans have 46 chromosomes. These come in pairs, so a person will have cells that contain 23 pairs of chromosomes. In Down syndrome, there are 47 chromosomes, with the additional genetic material coming from chromosome 21. For this reason, Down syndrome is also known as trisomy 21.
These mostly occur sporadically, however, in a minority of cases, Down Syndrome is caused by other genetic mechanisms such as translocation or mosaicism.
What are the health effects in a child who has Down Syndrome?
Children with Down syndrome can have a wide range of health outcomes, and these vary between individuals.
Some babies may be born with congenital anomalies, such as structural heart defects or gastrointestinal obstruction. Some defects require surgery after birth.
Other medical conditions associated with Down Syndrome include hearing loss, visual problems, learning disability, thyroid disease, increased risk of leukemia and early onset Alzheimer’s disease.
The intellectual or cognitive disability and other malformations in a child with Down Syndrome can vary significantly between individuals. Additionally, not all individuals are affected by all of these conditions.
During pregnancy, many fetuses with Down syndrome may have no visible structural abnormalities on ultrasound, particularly in early gestation. This is why prenatal screening, rather than ultrasound alone, plays an important role.
How common is Down Syndrome?
The risk of Down syndrome increases with maternal age, but it can occur at any age. Older maternal age is associated with a higher risk when compared to younger women. However, most women over 35 years of age still have babies with normal chromosomes. Additionally, younger women may have a lower risk, but Down Syndrome can still occur in this age group. For this reason, the age of the mother alone is not sufficient to determine risk, and screening is now offered to women of all ages.
Who should be screened for Down Syndrome?
Current guidelines recommend that all pregnant women, regardless of age, be offered information about prenatal screening and diagnostic testing for Down syndrome and other chromosomal conditions.
Each woman may choose to undergo screening, to proceed directly to diagnostic testing, or to decline testing altogether.
This decision is personal and may depend on individual risk assessment, how results influence pregnancy management, as well as personal beliefs, values and cultural background.
Your doctor can provide clear information and support informed decision-making.
What exactly is a screening test and what is the difference between screening and diagnostic testing?
A screening test evaluates whether a pregnancy is at increased risk for specific conditions and estimates that degree of risk. Screening does not provide information on all genetic abnormalities. Additionally, screening tests are not 100% effective which means that false positive and false negative results can occur. A false positive result suggests that the pregnancy is high risk, but upon confirmation, the pregnancy is found to be unaffected. Conversely, a false negative result indicates that the pregnancy is low risk, but the fetus is found to be affected by the condition tested.
If a screening test yields a high risk result, the next step to confirm the result would be a diagnostic test such as amniocentesis. For more information on prenatal diagnosis, click here.
What Prenatal Screening Options Are Available?
Currently there are multiple prenatal screening options available. These include testing the mother’s blood for analytes, ultrasound, a combination of both, or testing the mother’s blood for DNA fragments of the pregnancy. Below are a few options for prenatal screening.
1. Combined First-Trimester Screening.
The combined first trimester screening is a screening method that uses a combination of ultrasound and maternal blood testing. This is performed between 11 and 13+6 weeks of pregnancy and it includes a blood test of the mother to check for 2 analytes (b-hCG and PAPP-A), as well as performing a scan to measure the nuchal translucency of the fetus. The nuchal translucency is a fluid filled space at the back of the fetal neck and it can be thickened in fetuses with genetic abnormalities. For more information on the NT scan, click here.
When NT measurement is used alone, the detection rate for Down syndrome is approximately 70%. When combined with biochemical markers, detection improves to approximately 85–90%, with a 5% false-positive rate.
2. Second-Trimester Screening (Quadruple Test)
This second-trimester screening test is performed between 15 and 20 weeks gestation. A maternal blood sample is taken and tested for 4 analytes (alpha fetoprotein, hCG, unconjugated estriol and Inhibin A). These are then used to assess the risk of Down Syndrome in the fetus. The detection rate of the quadruple test is approximately 80%, which is lower than the first trimester test or the cfDNA.
3. Non-Invasive Prenatal Testing (NIPT)
This is more correctly known as the cell-free DNA (cfDNA) testing. A maternal blood sample is taken and sent to the lab to analyze DNA fragments from the placenta. This test assumes that the genetic makeup of the fetus and the placenta are identical (which is true in most, but not all cases). This test can be performed from 10 weeks of pregnancy onwards and is the test with the highest sensitivity and specificity currently available. For more information on the NIPT or cfDNA, click here.
Additionally, there are other tests which combine the first and second trimester screening tests, for increased sensitivity. However, they are less often used today with the introduction of cfDNA.
Whether someone decides to undergo screening or not, and which test they choose can depend on a variety of factors. As such, your doctor can help you by sharing more information to help you make a decision.
References
1. American College of Obstetricians and Gynecologists. Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin No. 226. Obstet Gynecol. 2020;136(4):e48-69. doi:10.1097/AOG.0000000000004084.
2. Salomon LJ, Alfirevic Z, Audibert F, et al. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice. Ultrasound Obstet Gynecol. 2014;44(4):484-9. doi:10.1002/uog.13393.
3. Cunningham FG, Leveno KJ, Dashe JS, Hoffman BL, Spong CY, Casey BM. Williams obstetrics. 26th ed. New York: McGraw-Hill Education; 2022.
Maternal–Fetal Medicine Specialist in Bangkok
Dr. Narisra Srikureja Firer, M.D. (Dr. Niti)
Dr. Niti is a Bangkok-based OBGYN with subspecialty training in Maternal–Fetal Medicine (MFM). She provides comprehensive care for women across all stages of life, including pregnancy care, deliveries, and general gynecological conditions.
She dedicates her time to private practice at Mission Hospital and serves as a Maternal–Fetal Medicine Consultant at a large government tertiary care center.
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